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In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.We are interested in developing a second generation of antibody-drug conjugates (ADCs) for the treatment of non-Hodgkin lymphoma (NHL) that could provide a longer duration of response and be more effective in indolent NHL than the microtubule-inhibiting ADCs pinatuzumab vedotin [anti-CD22-vc-monomethyl auristatin E (MMAE)] and polatuzumab vedotin (anti-CD79b-vc-MMAE). Pinatuzumab vedotin (anti-CD22-vc-MMAE) and polatuzumab vedotin (anti-CD79b-vc-MMAE) are ADCs that contain the microtubule inhibitor MMAE. Plumbagin Clinical trial data suggest that these ADCs have promising efficacy for the treatment of NHL; however, some patients do not respond or become resistant to the ADCs. We tested an anti-CD22 ADC with a seco-CBI-dimer payload, thio-Hu anti-CD22-(LCK149C)-SN36248, and compared it with pinatuzumab vedotin for its efficacy and duration of response in xenograft models and its ability to deplete normal B cells in cynomolgus monkeys. We found that anti-CD22-(LCK149C)-SN36248 was effective in xenograft models resistant to pinatuzumab vedotin, gave a longer duration of response, had a different mechanism of resistance, and was able to deplete normal B cells better than pinatuzumab vedotin. These studies provide evidence that anti-CD22-(LCK149C)-SN36248 has the potential for longer duration of response and more efficacy in indolent NHL than MMAE ADCs and may provide the opportunity to improve outcomes for patients with NHL.
Policies raising the minimum age of sale of tobacco products to 21 (T21) proliferated at state and local levels across the USA before a federal policy was adopted. Evidence of the effectiveness of these policies is building and lags implementation. This study exploits demographic patterns of cigarette brand purchasing to evaluate the effectiveness of T21.
To capture the effect of T21 implementation on cigarette sales, we used universal product code-level data from Nielsen Scantrack data covering January 2015 to October 2019. We used the 2015 to 2018 National Survey on Drug Use and Health to identify cigarette brands where smokers under 21 comprised a disproportionately high (young) and low (old) share of consumption. We fit fixed-effects linear regressions in Nielsen designated market areas to test if sales of young or old cigarette brands were changed by T21. Unadjusted models controlled for time and T21 implementation date. Adjusted models controlled for price, seasonality and unemployment. A permutation test of 5000 randomised placebo T21 policies were fit to determine how well the true date of implementation fit sales data stratified by brand group.
Sales of disproportionately young brands declined after T21 implementation. T21 policy implementation dates fit disproportionately young brand sales trends better than 99% of adjusted randomised placebo models. T21 implementation fit disproportionately old brand sales trends better than just 1% of adjusted randomised placebo models.
This study adds compelling empirical evidence that T21 decreased purchases of the cigarette brands consumed disproportionately by young people, the policy's target demographic.
This study adds compelling empirical evidence that T21 decreased purchases of the cigarette brands consumed disproportionately by young people, the policy's target demographic.
New Zealand's Smokefree 2025 goal aims to greatly decrease the availability of tobacco. One option is to cease the sale of tobacco from convenience stores. However, tobacco companies and retail trade associations oppose this move and have argued that customers who purchase tobacco drive footfall and spend more than non-tobacco customers. The aim of this study is to test the validity of industry claims about the importance of tobacco to convenience stores.
During November and December 2019, immediate postpurchase surveys were undertaken with customers on exit from a random sample of 100 convenience stores in two New Zealand cities. We estimated the mean number of items purchased, including tobacco and non-tobacco items, and mean expenditure on non-tobacco items.
Of the 3399 transactions recorded, 13.8% included tobacco, of which 8.3% comprised tobacco only and 5.5% included tobacco and non-tobacco items. The mean number of transactions containing both tobacco and non-tobacco items was 1.98, and 1.87 for those containing non-tobacco items only. Customers who purchased tobacco and non-tobacco items spent on average NZ$6.99 on non-tobacco items, whereas customers who purchased non-tobacco items only, spent on average NZ$5.07.
Our results do not support claims that tobacco drives one-quarter of footfall into stores or that customers who purchase tobacco spend almost twice as much as non-tobacco customers. Combined purchases of tobacco and non-tobacco items constituted 5.5% of transactions; the impact on a store's profitability of removing tobacco sales is unknown and could be the focus of future research.
Our results do not support claims that tobacco drives one-quarter of footfall into stores or that customers who purchase tobacco spend almost twice as much as non-tobacco customers. Combined purchases of tobacco and non-tobacco items constituted 5.5% of transactions; the impact on a store's profitability of removing tobacco sales is unknown and could be the focus of future research.
To elucidate the risk factors associated with resignation from work of Japanese women undergoing infertility treatment.
A total of 1727 female patients who attended a private fertility clinic in Japan participated in the Japan-Female Employment and Mental health in Assisted reproductive technology study. Questions related to demographic, clinical and socioeconomic characteristics were employed in the questionnaire. Out of the 1727 patients, 1075 patients who were working at the time of initiating infertility treatment and felt infertility treatment incompatible with work were included in the analysis. Risk factors for resignation were assessed by using multivariable logistic regression models.
Among 1075 working women who started infertility treatment, 179 (16.7%) subsequently resigned. Multivariable-adjusted ORs for resignation in those with lower educational background and infertility for ≥2 years were 1.58 (95% CI 1.07 to 2.34) and 1.82 (95% CI 1.15 to 2.89), respectively. The OR for resignation in non-permanent workers undergoing infertility treatment was 2.
My Website: https://www.selleckchem.com/products/plumbagin.html
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